To xxx on the work of Drs. Lerner and Cheney and others posted by Rich Van K
04/05/08 08:45 PM
Hi,
As far as I can tell, Dr. Lerner and Dr. Cheney are describing different heart conditions. Dr. Lerner focuses on viral cardiomyopathy that involves incomplete multiplication of Epstein-Barr virus or human cytomegalovirus in the heart muscle cells. He has documented this by biopsy of the heart muscle as well as by blood serum antibody testing and Holter monitor (24-hour recording electrocardiogram). He appears to have good evidence that the viruses are present in the heart muscle cells, but that they do not multiply normally, so that the rate of die-off of the cells is slower than for a runaway viral infection. This type of cardiomyopathy causes a gradual weakening of the heart muscle, and eventually leads to a dilated cardiomyopathy. The cardiac output goes down because the heart muscle is weak on the systolic or output stroke.
Dr. Cheney, on the other hand, describes a diastolic dysfunction, which is caused by an energy shortage in the heart muscle cells, due to too low a rate of production of ATP by the mitochondria. He documents this using advanced echocardiography that is capable of observing the detailed function of the parts of the heart. In this case, the cardiac output goes down because the heart muscle does not relax fast enough to allow enough blood to enter the left ventricle during the diastolic stroke. Dr. Cheney also describes a PFO (patent foramen ovale), and I think that is secondary to the diastolic dysfunction, because the latter changes the pressures in the chambers of the heart, which causes the PFO to be blown open.
I think these represent two different problems that can occur in the heart in CFS. In the situation described by Dr. Lerner, the viruses must be present in the body, and the immune system must be compromised to allow them to infect the heart, but still competent enough to prevent them from multi-plying normally. I would attribute this to glutathione depletion. I might note that Dr. Lerner read my poster paper at the IACFS meeting in January 2007, and he told me that he thought that it made sense. The paper included a description of reactivation of latent viruses and compromise of the immune system as a result of glutathione depletion and the methylation cycle block.
In the situation described by Dr. Cheney, as I wrote earlier, I think that de-pletion of glutathione in the heart muscle cells causes a decrease in the rate of ATP production, which leads to diastolic dysfunction. I don't think that viruses need to be present to cause this situation, but Dr. Cheney may believe that they are responsible for lowering the activation of the anti-oxidant enzymes, which is what he believes is responsible for the lowered rate of ATP production.
In summary, I think Drs. Lerner and Cheney are describing different phenomena in the heart in CFS, but I think both these phenomena result from glutathione depletion and the methylation cycle block.
I also believe that glutathione depletion and the methylation cycle block are at the root of the RNase-L elevation and fragmentation as well as the other immune dysfunctions emphasized by Dr. De Meirleir (though I don't think he agrees with this), and that glutathione depletion is the cause of the rise in peroxynitrite emphasized by Prof. Martin Pall (but he does not agree with this).
Furthermore, I think that chronic Lyme disease involves depletion of glutathione and glutathione peroxidase by the Borrelia bacteria, leading to a methylation block (I don't think the Lyme researchers agree with this, but probably most haven't heard of it yet). I also think that many cases of multiple chemical sensitivity are due to depletion of glutathione in the sustentacular cells of the olfactory epithelium, inside the nasal cavity, which explains why a glutathione nasal spray can bring relief (I haven't discussed this possibility with Dr. Grace Ziem, but I don't think Prof. Pall agrees with it).
I'm currently working on trying to find a link between Dr. Ritchie Shoemaker's biotoxin pathway and the pathogenesis mechanism in the GD-MCB hypothesis. Two candidates that I'm looking at are the effect of glutathione depletion in the pituitary on the production of proopio-melanocortin, from which both ACTH and MSH are produced (note that MSH is low in Dr. Shoemaker's model) and possible reaction between biotoxins and vitamin B12 when glutathione is depleted, so that B12 loses its normal protection (I don't have enough evidence yet to support a connection here).
I would also like to find the link to fibromyalgia, and at this point I'm looking at deficiency of myelin basic protein as a result of the methylation cycle block, and excitotoxicity, which is found in both CFS and FM. I'm considering the possibility that the folate trap that results from the block at methionine synthase frees up glutamic acid, which raises the ratio of glutamate to GABA and produces excitoxicity. The question arises as to why some people have one, some have the other, and some have both. I suspect that genetic variations will turn out to be the answer.
If more people who have pure fibromyalgia turn out to have success with treatment directed at lifting the methylation cycle block, it will give me more confidence that a link can be found between CFS and FM that involves the pathogenetic mechanism I have proposed for CFS.
If all this works out, we will have a "grand unified theory" for all these disorders, which either occur together or have very similar symptomatology. I hasten to add that we are not there yet, and I am probably the only researcher who thinks this approach is likely to work. But time will tell.
Best regards, Rich
